Dynamics of levitated nanospheres: towards the strong coupling regime

The use of levitated nanospheres represents a new paradigm for the optomechanical cooling of a small mechanical oscillator, with the prospect of realising quantum oscillators with unprecedentedly high quality factors. We investigate the dynamics of this system, especially in the so-called self-trapping regimes, where one or more optical fields simultaneously trap and cool the mechanical oscillator. The determining characteristic of this regime is that both the mechanical frequency $\omega_M$ and single-photon optomechanical coupling strength parameters $g$ are a function of the optical field intensities, in contrast to usual set-ups where $\omega_M$ and $g$ are constant for the given system. We also measure the characteristic transverse and axial trapping frequencies of different sized silica nanospheres in a simple optical standing wave potential, for spheres of radii $r=20-500$\,nm, illustrating a protocol for loading single nanospheres into a standing wave optical trap that would be formed by an optical cavity. We use this data to confirm the dependence of the effective optomechanical coupling strength on sphere radius for levitated nanospheres in an optical cavity and discuss the prospects for reaching regimes of strong light-matter coupling. Theoretical semiclassical and quantum displacement noise spectra show that for larger nanospheres with $r \gtrsim 100$\,nm a range of interesting and novel dynamical regimes can be accessed. These include simultaneous hybridization of the two optical modes with the mechanical modes and parameter regimes where the system is bistable. We show that here, in contrast to typical single-optical mode optomechanical systems, bistabilities are independent of intracavity intensity and can occur for very weak laser driving amplitudes

Inflammation in Metabolic Cardiomyopathy

Overlapping pandemics of lifestyle-related diseases pose a substantial threat to cardiovascular health. Apart from coronary artery disease, metabolic disturbances linked to obesity, insulin resistance and diabetes directly compromise myocardial structure and function through independent and shared mechanisms heavily involving inflammatory signals. Accumulating evidence indicates that metabolic dysregulation causes systemic inflammation, which in turn aggravates cardiovascular disease. Indeed, elevated systemic levels of pro-inflammatory cytokines and metabolic substrates induce an inflammatory state in different cardiac cells and lead to subcellular alterations thereby promoting maladaptive myocardial remodeling. At the cellular level, inflammation-induced oxidative stress, mitochondrial dysfunction, impaired calcium handling, and lipotoxicity contribute to cardiomyocyte hypertrophy and dysfunction, extracellular matrix accumulation and microvascular disease. In cardiometabolic patients, myocardial inflammation is maintained by innate immune cell activation mediated by pattern recognition receptors such as Toll-like receptor 4 (TLR4) and downstream activation of the NLRP3 inflammasome and NF-κB-dependent pathways. Chronic low-grade inflammation progressively alters metabolic processes in the heart, leading to a metabolic cardiomyopathy (MC) phenotype and eventually to heart failure with preserved ejection fraction (HFpEF). In accordance with preclinical data, observational studies consistently showed increased inflammatory markers and cardiometabolic features in patients with HFpEF. Future treatment approaches of MC may target inflammatory mediators as they are closely intertwined with cardiac nutrient metabolism. Here, we review current evidence on inflammatory processes involved in the development of MC and provide an overview of nutrient and cytokine-driven pro-inflammatory effects stratified by cell type

A method to quantify FRET stoichiometry with phasor plot analysis and acceptor lifetime ingrowth.

FRET is widely used for the study of protein-protein interactions in biological samples. However, it is difficult to quantify both the FRET efficiency (E) and the affinity (Kd) of the molecular interaction from intermolecular FRET signals in samples of unknown stoichiometry. Here, we present a method for the simultaneous quantification of the complete set of interaction parameters, including fractions of bound donors and acceptors, local protein concentrations, and dissociation constants, in each image pixel. The method makes use of fluorescence lifetime information from both donor and acceptor molecules and takes advantage of the linear properties of the phasor plot approach. We demonstrate the capability of our method in vitro in a microfluidic device and also in cells, via the determination of the binding affinity between tagged versions of glutathione and glutathione S-transferase, and via the determination of competitor concentration. The potential of the method is explored with simulations.This work was funded by grants from the Medical Research Council, the Wellcome Trust, the Alzheimer Research UK Trust, and the Engineering and Physical Sciences Research Council. W.Y.C. is funded by a China Scholarship Council-Cambridge Scholarship. D.R. is a Principal Research Fellow of the Wellcome Trust.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0006349515000752#

Growth differentiation factor-15 and prediction of cancer-associated thrombosis and mortality: a prospective cohort study

Background Patients with cancer are at increased risk of venous thromboembolism (VTE) and arterial thromboembolic/thrombotic events (ATEs). Growth differentiation factor-15 (GDF-15) improves cardiovascular risk assessment, but its predictive utility in patients with cancer remains undefined. Objectives To investigate the association of GDF-15 with the risks of VTE, ATE, and mortality in patients with cancer and its predictive utility alongside established models. Methods The Vienna Cancer and Thrombosis Study (CATS)—a prospective, observational cohort study of patients with newly diagnosed or recurrent cancer—which was followed for 2 years, served as the study framework. Serum GDF-15 levels at study inclusion were measured, and any association with VTE, ATE, and death was determined using competing risk (VTE/ATE) or Cox regression (death) modeling. The added value of GDF-15 to established VTE risk prediction models was assessed using the Khorana and Vienna CATScore. Results Among 1531 included patients with cancer (median age, 62 years; 53% men), median GDF-15 levels were 1004 ng/L (IQR, 654-1750). Increasing levels of GDF-15 were associated with the increased risks of VTE, ATE, and all-cause death ([subdistribution] hazard ratio per doubling, 1.16 [95% CI, 1.03-1.32], 1.30 [95% CI, 1.11-1.53], and 1.57 [95% CI, 1.46-1.69], respectively). After adjustment for clinically relevant covariates, the association only prevailed for all-cause death (hazard ratio, 1.21; 95% CI, 1.10-1.33) and GDF-15 did not improve the performance of the Khorana or Vienna CATScore. Conclusion GDF-15 is strongly associated with survival in patients with cancer, independent of the established risk factors. While an association with ATE and VTE was identified in univariable analysis, GDF-15 was not independently associated with these outcomes and failed to improve established VTE prediction models

Femoral head decentration on hip MRI: comparison between imaging planes, methods of contrast administration, and hip deformities.

OBJECTIVES To compare the prevalence of femoral head decentration (FHD) on different MR imaging planes in patients undergoing direct/indirect hip MR arthrography (MRA) with asymptomatic controls and to evaluate its association with osseous deformities. METHODS IRB-approved retrospective single-center study of symptomatic hips undergoing direct or indirect hip MRA at 3 T. Asymptomatic participants underwent non-contrast hip MRI at 3 T. FHD was defined as a continuous fluid layer between the acetabulum and femoral head and assessed on axial, sagittal and radial images. The association of intra-articular/intra-venous contrast agents and the prevalence of FHD was evaluated. The association of FHD with osseous deformities and joint damage was assessed using multiple logistic regression analysis. RESULTS Three-hundred ninety-four patients (447 hips, mean age 31 ± 9 years, 247 females) were included and compared to 43 asymptomatic controls (43 hips, mean age 31 ± 6 years, 26 females). FHD was most prevalent on radial images and more frequent in symptomatic hips (30% versus 2%, p < 0.001). FHD prevalence was not associated with the presence/absence of intra-articular contrast agents (30% versus 22%, OR = 1.5 (95% CI 0.9-2.5), p = 0.125). FHD was associated with hip dysplasia (OR = 6.1 (3.3-11.1), p < 0.001), excessive femoral torsion (OR = 3.0 (1.3-6.8), p = 0.010), and severe cartilage damage (OR = 3.6 (2.0-6.7), p < 0.001). CONCLUSION While rare in asymptomatic patients, femoral head decentration in symptomatic patients is associated with osseous deformities predisposing to hip instability, as well as with extensive cartilage damage. CRITICAL RELEVANCE STATEMENT Decentration of the femoral head on radial MRA may be interpreted as a sign of hip instability in symptomatic hips without extensive cartilage defects. Its presence could unmask hip instability and yield promise in surgical decision-making. KEY POINTS The best method of identifying femoral head decentration is radial MRI. The presence/absence of intra-articular contrast is not associated with femoral head decentration. Femoral head decentration is associated with hip deformities predisposing to hip instability

Localized actuation of temperature responsive hydrogel-layers with a PCB-based micro-heater array

Space-resolved stimulation of active hydrogel layers can be achieved for example by using a micro-heater array. In the current work, we present the interaction of (i) such a rigid array of heating elements that can be selectively activated and (ii) an active thermo-responsive hydrogel layer that responds to the local stimulus change. Due to the respective local actuation, (iii) the surface form of a passive top-layer can be manipulated. We present continuum-based simulative predictions based on the Temperature Expansion Model and compare them to experimental outcomes for the system

Hip MRI in flexion abduction external rotation for assessment of the ischiofemoral interval in patients with hip pain-a feasibility study.

OBJECTIVES To assess the feasibility of flexion-abduction-external rotation (FABER) magnetic resonance imaging (MRI) of the hip to visualize changes in the ischiofemoral interval and ability to provoke foveal excursion over the acetabular rim. METHODS IRB-approved retrospective single-center study. Patients underwent non-contrast 1.5-T hip MRI in the neutral and FABER position. Two readers measured the ischiofemoral interval at three levels: proximal/distal intertrochanteric distance and ischiofemoral space. Subgroup analysis was performed for hips with/without high femoral torsion, or quadratus femoris muscle edema (QFME), respectively. A receiver operating curve with calculation of the area under the curve (AUC) for the prediction of QFME was calculated. The presence of foveal excursion in both positions was assessed. RESULTS One hundred ten patients (121 hips, mean age 34 ± 11 years, 67 females) were evaluated. FABER-MRI led to narrowing (both p < .001) of the ischiofemoral interval which decreased more at the proximal (mean decrease by 26 ± 7 mm) than at the distal (6 ± 7 mm) intertrochanteric ridge. With high femoral torsion/ QFME, the ischiofemoral interval was significantly narrower at all three measurement locations compared to normal torsion/no QFME (p < .05). Accuracy for predicting QFME was high with an AUC of .89 (95% CI .82-.94) using a threshold of ≤ 7 mm for the proximal intertrochanteric distance. With FABER-MRI foveal excursion was more frequent in hips with QFME (63% vs 25%; p = .021). CONCLUSION Hip MRI in the FABER position is feasible, visualizes narrowing of the ischiofemoral interval, and can provoke foveal excursion. CRITICAL RELEVANCE STATEMENT FABER MRI may be helpful in diagnosing ischiofemoral impingement and detecting concomitant hip instability by overcoming shortcomings of static MR protocols that do not allow visualization of dynamic changes in the ischiofemoral interval and thus may improve surgical decision making. KEY POINTS • FABER MRI enables visualization of narrowing of the ischiofemoral interval proximal to the lesser trochanter. • Proximal intertrochanteric distance of ≤ 7 mm accurately predicts quadratus femoris muscle edema. • Foveal excursion was more frequent in hips with quadratus femoris muscle edema

Are degenerative findings detected on traction MR arthrography of the hip associated with failure of arthroscopic femoroacetabular impingement surgery?

OBJECTIVES To identify preoperative degenerative features on traction MR arthrography associated with failure after arthroscopic femoroacetabular impingement (FAI) surgery. METHODS Retrospective study including 102 patients (107 hips) undergoing traction magnetic resonance arthrography (MRA) of the hip at 1.5 T and subsequent hip arthroscopic FAI surgery performed (01/2016 to 02/2020) with complete follow-up. Clinical outcomes were assessed using the International Hip Outcome Tool (iHOT-12) score. Clinical endpoint for failure was defined as an iHOT-12 of < 60 points or conversion to total hip arthroplasty. MR images were assessed by two radiologists for presence of 9 degenerative lesions including osseous, chondrolabral/ligamentum teres lesions. Uni- and multivariate Cox regression analysis was performed to assess the association between MRI findings and failure of FAI surgery. RESULTS Of the 107 hips, 27 hips (25%) met at least one endpoint at a mean 3.7 ± 0.9 years follow-up. Osteophytic changes of femur or acetabulum (hazard ratio [HR] 2.5-5.0), acetabular cysts (HR 3.4) and extensive cartilage (HR 5.1) and labral damage (HR 5.5) > 2 h on the clockface were univariate risk factors (all p  2 h on the clockface (HR 3.2, p = 0.01), central femoral osteophyte (HR 3.1, p = 0.02), and femoral cartilage damage with ligamentum teres damage (HR 3.0, p = 0.04). CONCLUSION Joint damage detected by preoperative traction MRA is associated with failure 4 years following arthroscopic FAI surgery and yields promise in preoperative risk stratification. CLINICAL RELEVANCE STATEMENT Evaluation of negative predictors on preoperative traction MR arthrography holds the potential to improve risk stratification based on the already present joint degeneration ahead of FAI surgery. KEY POINTS • Osteophytes, acetabular cysts, and extensive chondrolabral damage are risk factors for failure of FAI surgery. • Extensive acetabular cartilage damage, central femoral osteophytes, and combined femoral cartilage and ligamentum teres damage represent independent negative predictors. • Survival rates following hip arthroscopy progressively decrease with increasing prevalence of these three degenerative findings

Occlusion of the infarct-related coronary artery presenting as acute coronary syndrome with and without ST-elevation: impact of inflammation and outcomes in a real-world prospective cohort

Background Patients with ST-segment elevation typically feature total coronary occlusion (TCO) of the infarct-related artery (IRA) on angiography, which may result in worse outcomes. Yet, relying solely on electrocardiogram (ECG) findings may be misleading and those presenting with non-ST-segment elevation acute coronary syndromes (NSTE-ACSs) may have TCO as well. Herein, we aimed to delineate clinical characteristics and outcomes of patients with ACS stratified by IRA location. Methods A total of 4787 ACS patients were prospectively recruited between 2009 and 2017 in SPUM-ACS (ClinicalTrials.gov Identifier: NCT01000701). The primary endpoint was major adverse cardiovascular events (MACEs), a composite of all-cause death, non-fatal myocardial infarction and non-fatal stroke at 1 year. Multivariable-adjusted survival models were fitted using backward selection. Results A total of 4412 ACS patients were included in this analysis, 56.0% (n = 2469) ST-elevation myocardial infarction (STEMI) and 44.0% (n = 1943) NSTE-ACS. The IRA was the right coronary artery (RCA) in 33.9% (n = 1494), the left-anterior descending coronary artery (LAD) in 45.6% (n = 2013), and the left circumflex (LCx) in 20.5% (n = 905) patients. In STEMI patients, TCO (defined as TIMI 0 flow at angiography) was observed in 55% of cases with LAD, in 63% with RCA, and in 55% with LCx. In those presenting with NSTE-ACS, TCO was more frequent in those with LCx and RCA as compared to the LAD (27 and 24%, respectively, vs. 9%, P &lt; 0.001). Among patients with NSTE-ACS, occlusion of the LCx was associated with an increased risk of MACE during 1 year after the index ACS (fully adjusted hazard ratio 1.68, 95% confidence interval 1.10–2.59, P = 0.02; reference: RCA and LAD). Features of patients with NSTE-ACS associated with TCO of the IRA included elevated lymphocyte and neutrophil counts, higher levels of high-sensitivity C reactive protein (hs-CRP) and high-sensitivity cardiac troponin T, lower eGFR, and notably a negative history of MI. Conclusion In NSTE-ACS, both LCx and RCA involvement was associated with TCO at angiography despite the absence of ST-segment elevation. Involvement of the LCx, but not the LAD or RCA, as the IRA represented an independent predictor of MACE during 1-year follow-up. Hs-CRP, lymphocyte, and neutrophil counts were independent predictors of total IRA occlusion, suggesting a possible role of systemic inflammation in the detection of TCO irrespective of ECG presentation